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Publication : RIF1 regulates early replication timing in murine B cells.

First Author  Malzl D Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  8049
PubMed ID  38081811 Mgi Jnum  J:362061
Mgi Id  MGI:7566766 Doi  10.1038/s41467-023-43778-y
Citation  Malzl D, et al. (2023) RIF1 regulates early replication timing in murine B cells. Nat Commun 14(1):8049
abstractText  The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of the genome. The best-known mechanism for controlling RT is the suppression of late origins of replication in heterochromatin by RIF1. Here, we report that in antigen-activated, hypermutating murine B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin and promotes early replication, but plays a minor role in regulating replication origin activity, gene expression and genome organization in B cells. Furthermore, we find that RIF1 functions in a complementary and non-epistatic manner with minichromosome maintenance (MCM) proteins to establish early RT signatures genome-wide and, specifically, to ensure the early replication of highly transcribed genes. These findings reveal additional layers of regulation within the B cell RT program, driven by the coordinated activity of RIF1 and MCM proteins.
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